Project Summary/Abstract
While there are many cancers that are in need of new therapeutic approaches, pediatric sarcomas are in a class
of their own. Five-year survival rates in these patients has held steady around 67% since 1990, without significant
improvements in the survival of the remaining 1/3 of patients since then. A major reason for the lack of progress
is the limited size of the market; there are only around 12,400 new cancers diagnosed in patients under 21 years
old each year in the U.S. In addition, drug development for pediatric patients require additional trials that account
for the different anatomy of children, metabolism, developmental stage and need for pediatric-friendly
formulations—such as liquid instead of tablets. The end result of these challenges is that out of 120 new cancer
drugs approved by the FDA between 1948 and 2002, only 30 of them—a paltry 25%—are used in children. Due
to this significant need, Shasqi, Inc. is focusing this SBIR project on applying its drug delivery technology towards
pediatric sarcomas. Sarcomas are typically treated with chemotherapies like doxorubicin, followed by surgical
resection of the tumor. Unfortunately, chemotherapies have severe side effects that can be quite severe and
result in death, which ultimately limits their use in young patients. On top of these side effects, doxorubicin can
cause myocardial toxicity that may ultimately lead to fatal congestive heart failure (CHF) during therapy or years
after termination of therapy, as well as secondary AML or myelodysplastic syndrome (MDS), which can also be
fatal diseases. There is clearly a great need to develop chemotherapies—and doxorubicin in particular—with
improved efficacy and improved therapeutic index, which would increase the success of tumor resection and
increase the survival of pediatric sarcoma patients. To overcome these adverse events while maintaining
efficacy, Shasqi is developing a patent-pending technology that utilizes an implantable biomaterial and prodrugs
of chemotherapeutics. Shasqi’s core technology is based on a bio-orthogonal ‘catch and release’ reaction
between the biomaterial and the prodrug that results in a localized payload release of the active
chemotherapeutic, avoiding systemic side effects. This approach combines the spatial control of injectable
biomaterials with the temporal control of systemic drug delivery, thus turning systemic drugs into localized
medicines. Under this project, Shasqi will tailor its biomaterial and doxorubicin prodrug towards pediatric
sarcoma tumors in three mouse studies: A tolerability study, a local quantification study, and a xenograft efficacy
study. The resulting data will provide critical data for IND-enabling studies as well as inform dosing strategies in
expanded efficacy studies in Phase II.